Project Summary/Abstract Climate change is causing a marked increase in ambient temperatures in specific regions, especially in US Midwest cities, leading to a heightened risk of heat-related illness (HRI). Notably, individuals' susceptibility to HRI severity and recovery varies due to several factors, including age, social determinants of health, and underlying health conditions. Given these variations, a personalized approach to risk management is imperative to mitigate the adverse consequences of HRI. This project will explore the effects of heat stress among at-risk populations including firefighters and elderly individuals residing in neighborhoods vulnerable to the effects of climate change using a combination of self-reported data, wearable sensors, and transcriptomic signatures in the following aims: Aim 1: Determine variation in severity of biometric responses and HRI in firefighters at the time of live burn training and its prediction of biometric measures during the week following exposure. Before, during, and for 3 h after training, core body temperature (CBT), heart rate (HR), and heart rate variability (HRV) will be measured in 24 firefighters. Neurological assessments will include fatigue/body discomfort and sleepiness surveys, postural balance, gait function and dual task tests. Whole blood and nasal swabs will be collected 1 week before, immediately after, and 3 days after exposure. Aim 2. Determine the association between exposure to elevated temperature and humidity and HRI among susceptible elderly individuals as measured by self- reported symptoms and smartwatch biometrics. A panel study will be conducted involving elderly individuals (>50yr, n=48) living in neighborhoods vulnerable to the effects of climate change due to poor tree canopy coverage, decreased community socioeconomic position and resources, and high percentage of racially marginalized populations. In-home temperature and humidity, weekly smartwatch biometrics and heat-related health questionnaires will be collected. Nasal swabs will be obtained for analysis in Aim 3. Aim 3. Determine whether nasal transcriptomic signatures can predict heat-related illness in individuals with increased susceptibility to climate change extreme heat. Changes in nasal transcriptomics will be assessed within-subject using specimens obtained before and after an extreme heat event [live burn training (Aim 1) or heat waves (Aim 2)]. RNA sequencing will be performed on firefighter whole blood and nasal and community member nasal specimens. Using biometric variables for classification, we will compare responders from non-responders with similar heat exposures and compare their transcriptomes. Understanding the transcriptomic signature of heat stress and its implications for both firefighters and vulnerable populations in heat-affected neighborhoods is of high significance and potential for public health impact. This research addresses the immediate health risks posed by rising temperatur...